The American Academy of Pediatrics’ new technical report on diagnosing and treating congenital toxoplasmosis (CT) underscores the specialized role that toxoplasmosis reference centers have in diagnosing suspected cases of CT. The report appeared in the journal Pediatrics.
This parasitic disease can be transmitted from mothers to infants and has the potential to cause serious health effects in utero and after birth. Transmission can occur in the event the mother acquires the infection either before or during a pregnancy. Women are at specific risk of developing CT if their immune systems become compromised, if they come into contact with a particularly virulent strain after consuming undercooked meat, or while traveling abroad. Although incidence rates of infection in the United States are actually quite low, most U.S. women of childbearing age have the potential to develop this infection.
As Deborah Lehman, MD, points out in her review of the new AAP report, “Consequences of maternal infection include hydrocephalus, sensorineural hearing loss, and developmental delay. Diagnosis and management of both pregnant women who may be infected and their infants is complex.” Lehman is the associate editor of the New England Journal of Medicine’s Journal Watch.
Persistence of Toxoplasma IgG antibodies in an infant more than 1-year-old is considered the “gold standard” criteria for diagnosing CT. Positive Toxoplasma IgG, IgM antibodies and/or positive Toxoplasma IgA antibodies are other indicators, as is positive Toxoplasma polymerase chain reaction (PCR) assay results from bodily fluids.
Diagnostic criteria also include “positive neonatal Toxoplasma IgG antibodies (but negative Toxoplasma IgM and IgA antibodies) and serologic evidence of acute maternal T gondii infection during pregnancy and evidence of clinical manifestations suggestive of CT,” according to the report.
The authors discuss the differences between reference and commercial laboratories in accurately detecting T. gondii infection through serologic testing. Toxoplasma IgG and IgM are among the most common tests commercial labs offer; some have PCR, Toxoplasma IgA and IgG-avidity tests as well.
Reference centers in Chicago and Palo Alto, California, offer combinations of the tests commercial labs provide, although they also conduct highly specialized tests such as the sensitive Toxoplasma IgM immunosorbent agglutination assay (ISAGA), as well as the Toxoplasma IgG dye test, and the Toxoplasma IgA enzyme-linked immunosorbent assay (ELISA).
Whereas commercial tests tend to vary in terms of sensitivity and specificity, “in reference laboratories, the specificity of the confirmatory testing (for the diagnosis of a recently acquired acute infection) is 100%,” according to the report’s authors.
In specifying diagnostic laboratory work-ups for fetuses and infants, the authors recommended that peripheral blood after birth for Toxoplasma IgG, IgM, and IgA should be delivered to commercial labs as soon as possible. Yet, they also recommended that toxoplasmosis reference laboratories handle cases of infants and women suspected of CT, as well as neonatal testing for toxoplasmosis.
“Negative Toxoplasma IgM ELISA at commercial hospital-based, clinic-based, or any other nonreference laboratories cannot exclude the diagnosis of CT, even in the absence of positive Toxoplasma IgA results,” the authors explained.
The report also outlines the laboratory work-ups for specific subtypes of toxoplasmosis, including Toxoplasma IgG, IgM ISAGA, IgA, and PCR. In the event of a positive test result for IgM or IgA, labs should redo the test 1 week after a final transfusion takes place to rule out the possibility of false positives that may been caused by a blood product transfusion or IV Ig infusion. The authors also suggested repeating these tests after birth if the infant’s blood potentially gets contaminated with the mother’s blood during labor.
“If maternal serologic test result was suggestive of an acute primary infection acquired very late in gestation, initially negative Toxoplasma IgM and IgA results at birth could also be attributable to delayed production of those antibodies, and repeat testing 2 to 4 weeks after birth and every 4 weeks thereafter until 3 months of age might be considered in such cases,” the report’s authors suggested.
In cases of suspected CT at birth, peripheral blood, urine, and cerebrospinal fluid Toxoplasma PCR tests should immediately take place. The report also discusses the different screening methods between the United States and Europe, and why there are fewer cases of symptomatic CT in Europe.
“Possible reasons for those disparities include differences in T gondii strains and the absence of antepartum screening and treatment of CT in the United States. In addition, differences between population-based, prospectively identified CT cases versus more selected cases referred to reference centers may bias reporting estimates,” the authors explained.